Smart Stimuli-Responsive and Mitochondria Targeting Delivery in Cancer Therapy

Abstract

Dysfunction in the mitochondria (Mc) contributes to tumor progression. It is a major challenge to deliver therapeutic agents specifically to the Mc for precise treatment. Smart drug delivery systems are based on stimuli-responsiveness and active targeting. Here, we give a whole list of documented pathways to achieve smart stimuli-responsive (St-) and Mc-targeted DDSs (St-Mc-DDSs) by combining St and Mc targeting strategies. We present the formulations, targeting characteristics of St-Mc-DDSs and clarify their anti-cancer mechanisms as well as improvement in efficacy and safety. St-Mc-DDSs usually not only have Mc-targeting groups, molecules (lipophilic cations, peptides, and aptamers) or materials but also sense the surrounding environment and correspondingly respond to internal biostimulators such as pH, redox changes, enzyme and glucose, and/or externally applied triggers such as light, magnet, temperature and ultrasound. St-Mc-DDSs exquisitely control the action site, increase therapeutic efficacy and decrease side effects of the drug. We summarize the clinical research progress and propose suggestions for follow-up research. St-Mc-DDSs may be an innovative and sensitive precision medicine for cancer treatment.

Progress in Nanocarriers Codelivery System to Enhance the Anticancer Effect of Photodynamic Therapy

“…In addition to targeting specific tissues, simultaneous targeting of multiple organelles has also been reported to have a stronger therapeutic effect. This can be achieved by combining PSs with different subcellular localization or by using different nanocarriers [27,43,44].…”

Multifunctional Mitochondria-Targeting Nanosystems for Enhanced Anticancer Efficacy

“…Although many mitochondria-targeting nanoparticles have been used to enhance cancer treatment, the leakage of drugs in cytoplasm and lysosome is challenging for all researchers when the therapeutic nanoparticles get inside the cancer cells ( Wong and Choi, 2015 ; Xiong et al, 2016 ; Huang et al, 2021 ). As we know, the pH value of tumor cell mitochondria is approximately 8.0 ( Matsuyama et al, 2000 ; Zhao et al, 2020 ).…”

Engineering defected 2D Pd/H-TiO2 nanosonosensitizers for hypoxia alleviation and enhanced sono-chemodynamic cancer nanotherapy

“…In view of the invasiveness, normal tissue damage and drug resistance that accompany surgery, chemotherapy, radiotherapy and targeted therapy [ 2 – 5 ], a therapeutic approach with remarkable efficacy and negligible side effects is desperately needed. The stimuli-responsive modalities initiated under the action of external and intratumoral incentives have been developing vigorously in cancer treatment owing to their site-confined lethality and controllability [ 6 – 8 ]. Wherein, sonodynamic therapy (SDT) is a burgeoning representative that takes ultrasound (US) as the external excitation source.…”